Retinal photoreceptors use dual pathways to tell brain ‘I’ve seen the light’

Key Takeaways

• ipRGCs, a type of photoreceptor that may be uniquely spared in glaucoma, uses two different pathways at the same time to transmit electrical “vision” signals to the brain.
• Such photoreceptors, according to the researchers, may have ancient origins on the evolutionary scale.

In animals, including humans, photoreceptors (light-sensing cells) called rods and cones are located in the retina, a tissue layer at the back of the eye that responds to light. The rods and cones are the primary photoreceptors for providing visual images of the environment together with their dynamic details such as motion, direction of movement, color, etc. (i.e., image-forming vision). The rods and cones analyze visual signals that are transmitted via electrical signals to the brain, which interprets what is “seen.”

Another type of photoreceptors in the retina, called intrinsically-photosensitive retinal ganglion cells (ipRGCs), serves a broad array of non-visual responses to light, including setting the body’s light-driven circadian rhythms and other subconscious bodily responses to ambient light. They also use long protrusions (axons) that form the optic nerve to convey visual signals from rods and cones, particularly with respect to distinguishing contrast and color.  While RGCs are generally the target of glaucoma, studies in rodent glaucoma models and glaucoma patients suggest that that ipRGCs may be uniquely spared. 

It has been known that photoreceptors in animals detect light by using a signaling pathway named for the cell’s origin. Photoreceptors of “microvillous” origin, similar to those in the fruit fly eye, use the enzyme phospholipase C to signal light detection—whereas photoreceptors of ciliary origin, such as those in our rods and cones, use a cyclic-nucleotide pathway. To signal light detection, most photoreceptors use either the microvillous or ciliary pathway, not both. 

In experiments to further understand how ipRGCs work, a team from Johns Hopkins Medicine found, to their surprise, that all six subtypes of ipRGCs use both pathways—although at different percentages—at the same time. The  team also found that while most photoreceptors using the ciliary signaling pathway use a signaling messenger called cGMP, ipRGCs use another, cAMP, which is similar to that used by jellyfish, an animal much older on the evolutionary scale. This suggests that ipRGCs may have an ancient origin. This and other findings, published in PNAS, “shed scientific as well as literal light” on a decades-long mystery about how such cells work, the researchers say. 

Edited by Miriam Kaplan, PhD

Sources:

Johns Hopkins University School of Medicine, Medical Xpress, January 25, 2024; see source article

Gao, J et al, “Intrinsically photosensitive retinal ganglion cells in glaucoma.” Frontiers in Cellular Neuroscience, September 23, 2022; doi: 10.3389/fncel.2022.992747